Brian Kobilka, MD, Professor, Department of Molecular and Cellular Physiology, Stanford University School of Medicine
Research description: The goal of Dr. Kobilka’s research over the past 25 years has been to characterize the structure and mechanism of activation of G protein coupled receptors (GPCRs). His lab has employed a variety of approaches including cell biology, gene disruption in mice, and in vivo physiology to determine the role of specific adrenergic receptor subtypes in normal physiology. During the past 15 years his group has applied a spectrum of biochemical and biophysical tools to study different aspects of GPCR structure and activation. These include the membrane protein crystallography, cryoelectron microscopy, NMR spectroscopy, double electron-electron resonance (DEER) spectroscopy, and fluorescence spectroscopy (both single-molecule and ensemble methods). His lab is currently working on several GPCRs known to play roles in carbohydrate and fat metabolism, or on insulin release including the M3 muscarinic receptor, the alpha-2 adrenergic receptor, beta-2 adrenergic receptor, glucagon receptor and the GLP1 receptor.
Selected relevant publications (Stanford DRC Members in BOLD):
1. Rasmussen SG, Devree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK & Kobilka BK. Crystal structure of the beta(2) adrenergic receptor-Gs protein complex. Nature 477, 549-555 (2011).
2. Kruse AC, Ring AM, Manglik A, Hu J, Hu K, Eitel K, Hübner K, Pardon E, Valant C, Sexton PM, Christopoulos A, Felder CC, Gmeiner P, Steyaert J, Weis WI, Garcia KC, Wess J, Kobilka, BK. Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature 504, 101-6 (2013).
3. Huang, W., Manglik, A., Venkatakrishnan, A.J., Laeremans, T., Feinberg, E.N., Sanborn, A.L., Kato, H.E., Livingston, K.E., Thorsen, T.S., Kling, R.C., Granier, S., Gmeiner, P., Husbands, S.M., Tryanor, J.R., Weis, W.I., Steyaert, J., Dror, R.O., Kobilika, B.K. Structural Insights into μ-opioid receptor activation. Nature 524, 315-321 (2015).
4. Nygaard, R., Zou, Y., Dror, R. O., Mildorf, T. J., Arlow, D. H., Manglik, A., Pan, A. C., Liu, C. W., Fung, J. J., Bokoch, M. P., Thian, F. S., Kobilka, T. S., Shaw, D. E., Mueller, L., Prosser, R. S. & Kobilka, B. K. The Dynamic Process of beta(2)-Adrenergic Receptor Activation. Cell 152, 532-542 (2013).
5. Manglik, A., Kim, T. H., Masureel, M., Altenbach, C., Yang, Z., Hilger, D., Lerch, M. T., Kobilka, T. S., Thian, F. S., Hubbell, W. L., Prosser, R. S., and Kobilka, B.K. Structural insights into the dynamic process of β2-adrenergic receptor signaling. Cell 161, 1101-1111 (2015).